The physiological actions of prostaglandin (PG)E2 are mediated through interaction with the prostaglandin E receptor(s). There are three subtypes of the EP receptor, EP1, EP2 and EP3 (for review see Coleman et al., 1989). These three subtypes all show high affinity for PGE2 but show differences in their affinities for various agonists and antagonists and exert their actions through different secondary transduction mechanisms. Thus activation of the EP1 receptor is associated with a rise in IP3 and intracellular calcium, activation of the EP2 receptor results in a rise in intracellular cyclic AMP and activation of the EP3 receptor a fall in intracellular cyclic AMP followed by a rise in intracellular calcium. To date the only members of this family to be cloned are the mouse EP2 (Honda et al., 1993) and the mouse EP3xcex1 and EP3xcex2 (Sugimoto et al., 1992; Sugimoto et al., 1993) subtypes. EP1 receptors are normally found on a wide variety of cells including the small intestine, kidney, stomach, muscle, eye, uterus and trachea, in humans and other animals. Binding of prostaglandin to the EP1 receptor protein elicits an increase in intracellular calcium levels. This signal causes the tissues to respond, for example, by muscle contraction.
A novel prostaglandin receptor protein termed EP1 has been identified from human cells. A DNA molecule encoding the full length EP1 protein has been isolated and purified, and the nucleotide sequence has been determined. The EP1 encoding DNA has been cloned into expression vectors and these expression vectors, when introduced into recombinant host cells, cause the recombinant host cells to express a functional EP1 receptor protein. The novel EP1 protein, the EP1-encoding DNA, the expression vectors and recombinant host cells expressing recombinant EP1 are useful in the identification of modulators of EP1 receptor activity.
A method of identifying EP1 receptor modulators is also disclosed which utilizes the recombinant EP1 expressing host cells. Modulators of EP1 activity are useful for the treatment of prostaglandin-related diseases and for modulating the effects of prostaglandin on the EP1 receptor.